Apparent reduced absorption of gemfibrozil when given with colestipol.
Colestipol and gemfibrozil may be used in combination to lower serum cholesterol and triglycerides. Since colestipol is known to bind certain anionic drugs, we studied the effect of colestipol on the pharmacokinetics of gemfibrozil in 10 patients with elevated serum cholesterol and triglycerides. Each patient received 600 mg of gemfibrozil by mouth during four different studies. Gemfibrozil was given randomly either alone, with, 2 hours before, or 2 hours after 5 grams of colestipol. The serum gemfibrozil concentration time curves were similar when gemfibrozil was given alone or two hours before or after colestipol. There was also no statistical difference in peak gemfibrozil concentration (Cmax), time to Cmax (tmax), area under the curve (AUC), or serum elimination half-life (t1/2) between any of these three treatments. However, when colestipol was given with gemfibrozil, there was a decrease in AUC (43.6 +/- 21.9 mg*hr/L) compared with gemfibrozil given alone (62.6 +/- 10.3 mg*hr/L) which was statistically different by both ANOVA and paired t-test. This finding suggests a decrease in gemfibrozil bioavailability. Cmax when colestipol was given with gemfibrozil (14.7 +/- 6.6 mg/L) was not statistically different from gemfibrozil alone (20.1 +/- 4.9 mg/L). However, the mean serum concentrations when gemfibrozil was given with colestipol were significantly lower at the 0.5, 1.0 and 1.5 hour sampling times when compared to the other regimens. Gemfibrozil serum elimination half-life was not significantly altered by combination with colestipol. The data suggest a reduction of gemfibrozil bioavailability when colestipol is administered concomitantly. Separating the administration of these two drugs by at least two hours will avoid this drug interaction.
Forland
S C
SC
Clinical Pharmacology Section, Loma Linda University Medical School, CA.
Feng
Y
Y
Cutler
R E
RE
D000368:Aged; D001682:Biological Availability; D002784:Cholesterol / Q000097:blood; D003084:Colestipol / Q000494:pharmacology*; D004347:Drug Interactions; D015248:Gemfibrozil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy; D007408:Intestinal Absorption / Q000187:drug effects; D008875:Middle Aged; D011073:Polyamines / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D011073:Polyamines; D014280:Triglycerides; D002784:Cholesterol; D003084:Colestipol; D015248:Gemfibrozil